1. Technical Field of the Invention
The present invention relates to the treatment or prevention of heart failure by inhibiting mast cell degranulation and, more especially, to a regimen for the pharmacological inhibition of adverse ventricular remodeling and development of heart failure via administration of mast cell stabilizing active species.
2. Description of the Prior Art
It is known to the art that a direct relationship exists between collagenase activity and the number of cardiac mast cells.
Too, the mast cell enzymes trypsin and stromelysin have been shown to activate latent interstitial collagenase in skin, producing extracellular matrix degradation.
Cf. Estensen, "What is the Role of Myocardial Mast Cells," Human Pathol., 16, No. 6, pp. 536-538 (1985); Kovanen et al., "Infiltrates of Activated Mast Cells at the Site of Coronary Atheromatous Erosion or Rupture in Myocardial Infarction," Circulation, 92, No. 5, pp. 1084-1088 (1995).
Human heart mast cells have also been characterized in Patella et al., "Human Heart Mast Cells, Isolation, Purification, Ultrastructure and Immunologic Characterization," J. Immunol., 154, pp. 2855-2865 (1995), and in Patella et al., "Immunologic and non-immunologic release of histamine and tryptase from human heart mast cells," Inflamma. Res., 44, Supp. I: S22-S23 (1995).
And "Activation of precursors for matrix metalloproteinases 1 (interstitial collagenase) and 3 (stromelysin) by rat mast-cell proteinases I and II" is described in Suzuki et al., Biochem. J., 305, pp. 301-306 (1995), as is "Effect of preliminary administration of alpha-tocopherol and intal on the course of experimental myocardial necrosis," Kardiologia, 29(4), pp. 94-96 (1989).
The effect of cromolyn sodium on necrosis in the first 4 days following myocardial infarction in rats is described in Amatuni et al., "The Effect of alpha-tocopherol and Intal on heart capillary bed and lipid peroxide oxidation in experimental necrosis of the rat myocardium," Cor-Vasa., 31(6), pp. 500-507 (1989).